Differential vasomotor effects of insulin on gastrocnemius and soleus feed arteries in the OLETF rat model: role of endothelin-1.

The vascular actions of insulin are complex, because it can stimulate both nitric oxide-mediated dilatation and endothelin (ET)-1-mediated constriction. We examined vasoreactivity to insulin in isolated feed arteries of the gastrocnemius (GFA) and soleus muscles (SFA) of 32-week-old Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats, a hyperphagic rodent model of obesity and insulin resistance. The insulin-induced vasoreactivity of SFA and GFA was similar in LETO (healthy) and OLETF (obese/insulin-resistant) rats. However, examination of between-vessel effects revealed a number of novel insights into the heterogeneous vascular effects of insulin. Soleus feed arteries dilated more than GFA in LETO at 100 and 1000 μIU ml(-1) insulin (23 versus 6 and 28 versus 0%, respectively; P < 0.05 for between-vessel differences). Likewise, in OLETF rats there was significantly greater dilatation in SFA than GFA at 10, 100 and 1000 μIU ml(-1) insulin (28 versus 3, 30 versus 0 and 34 versus 0%, respectively; all P < 0.05). In the presence of 3 μm tezosentan, a non-specific endothelin-1 receptor blocker, insulin-induced dilatation of the GFA was enhanced such that differences between vessels were largely abolished in both groups. Furthermore, acetylecholine-induced dilatation was significantly greater in SFA than GFA within each group, whereas sodium nitroprusside-induced dilatory responses were greater in the GFA compared with the SFA. Overall, our findings indicate that the insulin/endothelin-1 vasoconstrictor pathway is more active in GFA than in SFA, independent of obesity in the OLETF rat model.